Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Mitogens

Naquotinib

Protein Kinase Inhibitors

Enzyme Inhibitors

ASP8273

Medical Director

Purpose of the study is to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

* the safety and tolerability of ASP8273.
* the pharmacokinetics (PK) of ASP8273.
* the antitumor activity of ASP8273.

This study consists of Phase I and Phase II.

The objectives of Phase I are to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

* safety and tolerability of ASP8273.
* the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of ASP8273 based on the dose limiting toxicity (DLT) profile.
* pharmacokinetics (PK) of ASP8273.
* antitumor activity of ASP8273.

The objectives of Phase II are to determine the following at the RP2D of ASP8273 in patients with NSCLC harboring EGFR mutation.

* efficacy of ASP8273
* safety of ASP8273
* PK of ASP8273

An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations

An Open-label Study of the Oral Administration of ASP8273 in Patients With Non-small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor (EGFR) Mutations

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

A DLT is defined as any pre-determined toxicity that is related to study drug per the investigator and which occurs during Cycle 0 and Cycle 1 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE ver 4.0 - JCOG)

The overall response rate, which is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated

An AE is defined as any untoward medical occurrence in a subject administered a study drug or has undergone study procedures and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product

Laboratory tests to be conducted are hematology, biochemistry, urinalysis, coagulation profile, lipid panel and lymphocyte subpopulation

Vital signs to be measured includes blood pressure, pulse rate and temperature

The overall response rate is defined as the proportion of subjects whose best overall response is rated as complete response (CR) or partial response (PR) according to RECIST Version 1.1, will be calculated

The disease control rate is defined as the proportion of subjects whose best overall response is rated as CR, PR, or stable disease (SD) according to RECIST Version 1.1, will be calculated.

Astellas Pharma Inc

Symptoms and General Pathology

Recurrence

Amino Acids

Ibrutinib

Tyrosine Kinase Inhibitors

Tyrosine

Participants in Part 1 receive dose level of Ibrutinib depending on study joined. First group of participants receive lowest dose level of Ibrutinib. Each new group receives a higher dose of Ibrutinib than the group before it, if no intolerable side effects were seen. This continues until highest tolerable dose of Ibrutinib is found.

Participants in Part 2 receive Ibrutinib at highest dose that was tolerated in Part 1 or 840 mg daily.

Starting level of Ibrutinib: 560 mg by mouth daily in a 28 day cycle.

Part 1 Starting level of Ibrutinib: 560 mg by mouth daily in a 28 day cycle.

Part 2 Starting level of Ibrutinib: Maximum tolerated dose from Part 1 or 840 mg daily.

John Heymach, MD, PHD

The goal of Part 1 of this clinical research study is to find the highest dose of (Imbruvica) ibrutinib that can be given to patients with non-small cell lung cancer (NSCLC). The goal of Part 2 of this clinical research study is to learn if the dose of ibrutinib found in Part 1 can help to control the disease.

The safety of this drug will also be studied in both parts of the study.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of up to 6 participants will be enrolled in Part 1 of the study, and up to19 participants will be enrolled in Part 2.

If you are enrolled in Part 1, the dose of ibrutinib you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of ibrutinib. Each new group will receive a higher dose of ibrutinib than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of ibrutinib is found.

If you are enrolled in Part 2, you will receive ibrutinib at the highest dose that was tolerated in Part 1.

Study Drug Administration:

You will take ibrutinib pills 1 time each day, at about the same time every day. You may take your dose of ibrutinib with or without food.

Study Visits:

Each cycle is 4 weeks.

On Day 1 of all cycles:

* You will have a physical exam
* Blood (about 3 teaspoons) will be drawn for routine tests.
* On Cycle 2 only, blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing before your dose and then 4 more times over the next 6 hours after your dose. PK testing measure the amount of study drug in the body at different timepoints.
* If you the doctor thinks it is needed, blood (about ½ teaspoon) or urine will be collected for pregnancy testing.

Every 8 weeks, you will have a CT, MRI, or x-ray to check the status of the disease. You will have the same type of scan performed as you did at screening.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over after the follow-up visits.

End-of-Dosing Visit:

About 30 days after your last dose of study drug:

* You will have a physical exam.
* Blood (about 3 teaspoons) will be drawn for routine tests.
* If you the doctor thinks it is needed, blood (about ½ teaspoon) or urine will be collected for pregnancy testing.

Follow Up Visits:

Every 6 months you will be asked to come into the clinic or you will be called by a member of the study staff to ask how you are doing and if you have started any new anti-cancer treatments. If you are called, it should take about 10 minutes.

This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). It is considered investigational to use this drug to treat NSCLC. The study doctor can explain how the study drug is designed to work.

Up to 43 participants will be enrolled on this study. All will take part at MD Anderson.

A Phase I/II Study of Ibrutinib in Previously Treated Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer

Number of DLT observed at dose levels 560 (starting dose) and 840 mg PO daily to determine the MTD using the 3+3 design.

Complete response and partial resopnse rate RECIST 1.1 criteria The response was evaluated after two cycles of therapy and every 8 weeks until the first date that recurrent or progressive disease is objectively documented, up to 2 years.

Overall survival (OS) is defined as the duration of time from start of treatment to time of progression or death.

Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

Pharmacyclics LLC.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Participants received Ibrutinib at dose level 0 (560 mg PO daily)

Ibrutinib at Dose Level 0 (560 PO Daily).

Participants received Ibrutinib at dose level 1 (840 mg PO daily)

Ibrutinib at Dose Level 1 (840 PO Daily).

Participants received Ibrutinib at dose level 0 (560 mg PO daily on a continuous basis on 28 day cycles.

Ibrutinib Dose Level 0

Participants received Ibrutinib dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.

Ibrutinib Dose Level 1

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. John V. Heymach, Chair, Thoracic-Head & Neck Med Onc

Participants received Ibrutinib at dose level 0 (560 mg PO daily) on a continuous basis on 28 day cycles.

Ibrutinib Dose Level 0 (560mg)

Participants received Ibrutinib at dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.

Ibrutinib Dose Level 1 (840mg)

12 patients were evaluable for overall response rate; 1 patient who received 840 mg PO daily was inevaluable due to death prior to first response assessment after start of treatment.

Number of Participants With at Least One Dose Limiting Toxicity (DLT) Observed During the Dose Escalation to Determine the Maximum Tolerated Dose (MTD)

Participants received ibrutinib at dose level 0 (560 mg daily).

Participants received Ibrutinib at dose level 1 ( 840 mg PO daily).

Overall Response Rate in Patients With EGFR Mutations Using RECIST

Participants received Ibrutinib at dose level 0 (560 mg PO daily, starting dose) and dose level 1 (840 mg PO daily).

Participants received Ibrutinib at dose level 1 (840 mg PO daily).

13 patients were followed up 12 patients were evaluable for disease control rate, duration of response and Response rate in patients with HER2 mutant non-small cell lung cancer; 1 patient who received 840 mg PO daily was inevaluable due to death prior to first response assessment after start of treatment.

Overall Survival (OS)

Participants received Ibrutinib at dose level 0 (560 mg PO daily, starting dose).

Participants received Ibrutinib at dose level 1 (840 mg PO daily, starting dose).

Progression-Free Survival (PFS)

Participants received dose level 1 (840 mg PO daily) on a continuous basis on 28 day cycles.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
An Open Study of ASP8273 in Patients With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations	NCT02192697	Non-small Cell ...	ASP8273	20 Years -	Astellas Pharma Inc
A Phase I/II Study of Ibrutinib in Previously Treated Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer	NCT02321540	Lung Cancer	Ibrutinib	18 Years -	M.D. Anderson Cancer Center
A Phase I/II Study of Ibrutinib in Previously Treated Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer	NCT02321540	Lung Cancer	Ibrutinib	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for epidermal growth factor receptor mutations